Spatio-temporal analysis of prostate tumors in situ suggests pre-existence of treatment-resistant clones

The molecular mechanisms underlying lethal castration-resistant prostate cancer remain poorly understood, with intratumoral heterogeneity a likely contributing factor. To examine the temporal aspects of resistance, we analyze tumor heterogeneity in needle biopsies collected before and after treatmen...

Celý popis

Uloženo v:
Podrobná bibliografie
Vydáno v:Nature communications Ročník 13; číslo 1; s. 5475 - 18
Hlavní autoři: Marklund, Maja, Schultz, Niklas, Friedrich, Stefanie, Berglund, Emelie, Tarish, Firas, Tanoglidi, Anna, Liu, Yao, Bergenstråhle, Ludvig, Erickson, Andrew, Helleday, Thomas, Lamb, Alastair D., Sonnhammer, Erik, Lundeberg, Joakim
Médium: Journal Article
Jazyk:angličtina
Vydáno: London Nature Publishing Group UK 17.09.2022
Nature Publishing Group
Nature Portfolio
Témata:
13
38
45/77
631/61/212/2019
631/67/2329
631/67/589/466
631/67/69
692/53/2422
82/1
Androgen Antagonists - pharmacology
Androgen Antagonists - therapeutic use
Androgen receptors
Androgens
Androgens - metabolism
Biopsy
Castration
Clone Cells - metabolism
Clusters
Data analysis
Deprivation
Gene expression
Heterogeneity
Humanities and Social Sciences
Humans
Localization
Male
Molecular modelling
multidisciplinary
Populations
Prostate cancer
Prostatic Neoplasms - drug therapy
Prostatic Neoplasms - genetics
Prostatic Neoplasms - metabolism
Quorum sensing
Receptors
Receptors, Androgen - genetics
Receptors, Androgen - metabolism
Science
Science (multidisciplinary)
Spatial heterogeneity
Spatio-Temporal Analysis
Stromal cells
Transcriptomes
Transcriptomics
Tumors
ISSN:2041-1723, 2041-1723
On-line přístup:Získat plný text
Tagy: Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
Popis
Shrnutí:The molecular mechanisms underlying lethal castration-resistant prostate cancer remain poorly understood, with intratumoral heterogeneity a likely contributing factor. To examine the temporal aspects of resistance, we analyze tumor heterogeneity in needle biopsies collected before and after treatment with androgen deprivation therapy. By doing so, we are able to couple clinical responsiveness and morphological information such as Gleason score to transcriptome-wide data. Our data-driven analysis of transcriptomes identifies several distinct intratumoral cell populations, characterized by their unique gene expression profiles. Certain cell populations present before treatment exhibit gene expression profiles that match those of resistant tumor cell clusters, present after treatment. We confirm that these clusters are resistant by the localization of active androgen receptors to the nuclei in cancer cells post-treatment. Our data also demonstrates that most stromal cells adjacent to resistant clusters do not express the androgen receptor, and we identify differentially expressed genes for these cells. Altogether, this study shows the potential to increase the power in predicting resistant tumors. Spatial heterogeneity in prostate cancer can contribute to its resistance to androgen deprivation therapy (ADT). Here, the authors analyse prostate cancer samples before and after ADT using Spatial Transcriptomics, and find heterogeneous pre-treatment tumour cell populations and stromal cells that are associated with resistance.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-022-33069-3